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The genetics of Tourette syndrome

Nature Reviews Neurology volume 8, pages 203–213 (2012)Cite this article

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Abstract

Tourette syndrome is a complex neurological disorder that usually becomes evident between 4 and 18 years of age. The disorder is characterized by chronic motor and phonic tics, often with a variety of behavioural comorbidities; in particular, attention-deficit hyperactivity disorder, obsessive–compulsive disorder, and impulse control disorder. The cause of Tourette syndrome is poorly understood. Although environmental factors are proposed to have a role, genetic factors are thought to be the primary contributors to the pathogenesis of this disorder. However, identification of the causative gene mutations or risk alleles has proved to be difficult. Early studies on the genetics of Tourette syndrome focused on multigenerational lineages and suggested Mendelian inheritance, but subsequent segregation analyses point to a more-complex inheritance pattern. A monogenic inheritance model has been proposed following the identification of rare genetic mutations associated with the Tourette syndrome phenotype. Although no specific mutations have found to directly cause Tourette syndrome, genetic findings may enable identification of the affected pathways, and could lead to the development of new treatment strategies. In this Review, we provide an overview of the genetics of Tourette syndrome and highlight how this knowledge has improved our understanding of the possible pathogenic mechanisms of this neurological disorder.

Key Points

  • Tourette syndrome is a complex neurological disorder characterized by chronic motor and phonic tics, often accompanied by a variety of behavioural comorbidities

  • Genetics seem to have the most critical role in the aetiopathogenesis of Tourette syndrome, but the disorder may occur as the result of complex interactions between environmental and genetic factors

  • Cytogenetic and linkage analyses have uncovered a number of loci and several genetic mutations that are associated with Tourette syndrome

  • Discoveries of genetic mutations associated with the Tourette syndrome phenotype support the conclusion that the disorder has an autosomal dominant inheritance pattern

  • The genetic variants associated with Tourette syndrome may have important cumulative effects and could contribute to the phenotypic variability observed in patients with this disorder

  • Genetic findings have led to a better understanding of the possible pathogenic mechanisms of Tourette syndrome, which may guide the development of new treatment strategies

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Figure 1: Neuronal location and proposed function of gene products associated with Tourette syndrome.

References

  1. Jankovic, J. & Kurlan, R. Tourette syndrome: evolving concepts. Mov. Disord. 26, 1149–1156 (2011).

    PubMed  Google Scholar 

  2. Kurlan, R. Clinical practice. Tourette's syndrome. N. Engl. J. Med. 363, 2332–2338 (2010).

    CAS  PubMed  Google Scholar 

  3. Jankovic, J. Tourette's syndrome. N. Engl. J. Med. 345, 1184–1192 (2001).

    CAS  PubMed  Google Scholar 

  4. Cheung, M. Y., Shahed, J. & Jankovic, J. Malignant Tourette syndrome. Mov. Disord. 22, 1743–1750 (2007).

    PubMed  Google Scholar 

  5. Jankovic, J., Gelineau-Kattner, R. & Davidson, A. Tourette's syndrome in adults. Mov. Disord. 25, 2171–2175 (2010).

    PubMed  Google Scholar 

  6. Robertson, M. M. The prevalence and epidemiology of Gilles de la Tourette syndrome. Part 1: the epidemiological and prevalence studies. J. Psychosom. Res. 65, 461–472 (2008).

    PubMed  Google Scholar 

  7. Centers for Disease Control and Prevention (CDC). Prevalence of diagnosed Tourette syndrome in persons aged 6–17 years—United States (2007). MMWR Morb. Mortal. Wkly Rep. 58, 581–585 (2009).

  8. State, M. W. The genetics of Tourette disorder. Curr. Opin. Genet. Dev. 21, 302–309 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Jankovic, J. Treatment of hyperkinetic movement disorders. Lancet Neurol. 8, 844–856 (2009).

    CAS  PubMed  Google Scholar 

  10. Robertson, M. M. Tourette syndrome, associated conditions and the complexities of treatment. Brain 123, 425–462 (2000).

    PubMed  Google Scholar 

  11. Olson, S. Making sense of Tourette's. Science 305, 1390–1392 (2004).

    PubMed  Google Scholar 

  12. Paschou, P. et al. Indications of linkage and association of Gilles de la Tourette syndrome in two independent family samples: 17q25 is a putative susceptibility region. Am. J. Hum. Genet. 75, 545–560 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Khalifa, N. & von Knorring, A. L. Tourette syndrome and other tic disorders in a total population of children: clinical assessment and background. Acta Paediatr. 94, 1608–1614 (2005).

    PubMed  Google Scholar 

  14. Pauls, D. L., Raymond, C. L., Stevenson, J. M. & Leckman, J. F. A family study of Gilles de la Tourette syndrome. Am. J. Hum. Genet. 48, 154–163 (1991).

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Pauls, D. L., Cohen, D. J., Heimbuch, R., Detlor, J. & Kidd, K. K. Familial pattern and transmission of Gilles de la Tourette syndrome and multiple tics. Arch. Gen. Psychiatry 38, 1091–1093 (1981).

    CAS  PubMed  Google Scholar 

  16. Parraga, H. C., Parraga, M. I., Spinner, L. R., Kelly, D. P. & Morgan, S. L. Clinical differences between subjects with familial and non-familial Tourette's syndrome: a case series. Int. J. Psychiatry Med. 28, 341–351 (1998).

    CAS  PubMed  Google Scholar 

  17. Hyde, T. M., Aaronson, B. A., Randolph, C., Rickler, K. C. & Weinberger, D. R. Relationship of birth weight to the phenotypic expression of Gilles de la Tourette's syndrome in monozygotic twins. Neurology 42, 652–658 (1992).

    CAS  PubMed  Google Scholar 

  18. Price, R. A., Kidd, K. K., Cohen, D. J., Pauls, D. L. & Leckman, J. F. A twin study of Tourette syndrome. Arch. Gen. Psychiatry 42, 815–820 (1985).

    CAS  PubMed  Google Scholar 

  19. Grados, M. A., Mathews, C. A. & Tourette Syndrome Association International Consortium for Genetics. Latent class analysis of Gilles de la Tourette syndrome using comorbidities: clinical and genetic implications. Biol. Psychiatry 64, 219–225 (2008).

    PubMed Central  PubMed  Google Scholar 

  20. Voelker, R. Scientists use neuroimaging, genetic studies to probe biology of Tourette syndrome. JAMA 292, 909–911 (2004).

    CAS  PubMed  Google Scholar 

  21. Baron, M., Shapiro, E., Shapiro, A. & Rainer, J. D. Genetic analysis of Tourette syndrome suggesting major gene effect. Am. J. Hum. Genet. 33, 767–775 (1981).

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Curtis, D., Robertson, M. M. & Gurling, H. M. Autosomal dominant gene transmission in a large kindred with Gilles de la Tourette syndrome. Br. J. Psychiatry 160, 845–849 (1992).

    CAS  PubMed  Google Scholar 

  23. Pauls, D. L. & Leckman, J. F. The inheritance of Gilles de la Tourette's syndrome and associated behaviors. Evidence for autosomal dominant transmission. N. Engl. J. Med. 315, 993–997 (1986).

    CAS  PubMed  Google Scholar 

  24. State, M. W. The genetics of child psychiatric disorders: focus on autism and Tourette syndrome. Neuron 68, 254–269 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Kurlan, R., Eapen, V., Stern, J., McDermott, M. P. & Robertson, M. M. Bilineal transmission in Tourette's syndrome families. Neurology 44, 2336–2342 (1994).

    CAS  PubMed  Google Scholar 

  26. Walkup, J. T. et al. Family study and segregation analysis of Tourette syndrome: evidence for a mixed model of inheritance. Am. J. Hum. Genet. 59, 684–693 (1996).

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Ercan-Sencicek, A. G. et al. L-histidine decarboxylase and Tourette's syndrome. N. Engl. J. Med. 362, 1901–1908 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Singer, H. S. Tourette's syndrome: from behaviour to biology. Lancet Neurol. 4, 149–159 (2005).

    PubMed  Google Scholar 

  29. Hanna, P. A., Janjua, F. N., Contant, C. F. & Jankovic, J. Bilineal transmission in Tourette syndrome. Neurology 53, 813–818 (1999).

    CAS  PubMed  Google Scholar 

  30. Lichter, D. G., Dmochowski, J., Jackson, L. A. & Trinidad, K. S. Influence of family history on clinical expression of Tourette's syndrome. Neurology 52, 308–316 (1999).

    CAS  PubMed  Google Scholar 

  31. McMahon, W. M. et al. Bilineal transmission and phenotypic variation of Tourette's disorder in a large pedigree. J. Am. Acad. Child. Adolesc. Psychiatry 35, 672–680 (1996).

    CAS  PubMed  Google Scholar 

  32. Singer, H. S. Tourette syndrome and other tic disorders. Handb. Clin. Neurol. 100, 641–657 (2011).

    PubMed  Google Scholar 

  33. Petek, E. et al. Disruption of a novel gene (IMMP2L) by a breakpoint in 7q31 associated with Tourette syndrome. Am. J. Hum. Genet. 68, 848–858 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Verkerk, A. J. et al. CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder. Genomics 82, 1–9 (2003).

    CAS  PubMed  Google Scholar 

  35. Abelson, J. F. et al. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science 310, 317–320 (2005).

    CAS  PubMed  Google Scholar 

  36. Lawson-Yuen, A., Saldivar, J. S., Sommer, S. & Picker, J. Familial deletion within NLGN4 associated with autism and Tourette syndrome. Eur. J. Hum. Genet. 16, 614–618 (2008).

    CAS  PubMed  Google Scholar 

  37. Poliak, S. et al. Caspr2, a new member of the neurexin superfamily, is localized at the juxtaparanodes of myelinated axons and associates with K+ channels. Neuron 24, 1037–1047 (1999).

    CAS  PubMed  Google Scholar 

  38. Proenca, C. C., Gao, K. P., Shmelkov, S. V., Rafii, S. & Lee, F. S. Slitrks as emerging candidate genes involved in neuropsychiatric disorders. Trends Neurosci. 34, 143–153 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Bruses, J. L. Identification of gene transcripts expressed by postsynaptic neurons during synapse formation encoding cell surface proteins with presumptive synaptogenic activity. Synapse 64, 47–60 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Jamain, S. et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat. Genet. 34, 27–29 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  41. Furuta, K., Ichikawa, A., Nakayama, K. & Tanaka, S. Membrane orientation of the precursor 74-kDa form of L-histidine decarboxylase. Inflamm. Res. 55, 185–191 (2006).

    CAS  PubMed  Google Scholar 

  42. O'Rourke, J. A., Scharf, J. M., Yu, D. & Pauls, D. L. The genetics of Tourette syndrome: a review. J. Psychosom. Res. 67, 533–545 (2009).

    PubMed Central  PubMed  Google Scholar 

  43. Ezugha, H. et al. Microarray analysis in children with developmental disorder or epilepsy. Pediatr. Neurol. 43, 391–394 (2010).

    PubMed  Google Scholar 

  44. Ringman, J. M. & Jankovic, J. Occurrence of tics in Asperger's syndrome and autistic disorder. J. Child. Neurol. 15, 394–400 (2000).

    CAS  PubMed  Google Scholar 

  45. Boghosian-Sell, L., Comings, D. E. & Overhauser, J. Tourette syndrome in a pedigree with a 7;18 translocation: identification of a YAC spanning the translocation breakpoint at 18q22.3. Am. J. Hum. Genet. 59, 999–1005 (1996).

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Kroisel, P. M. et al. Candidate region for Gilles de la Tourette syndrome at 7q31. Am. J. Med. Genet. 101, 259–261 (2001).

    CAS  PubMed  Google Scholar 

  47. Burri, L. et al. Mature DIABLO/Smac is produced by the IMP protease complex on the mitochondrial inner membrane. Mol. Biol. Cell 16, 2926–2933 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Petek, E. et al. Molecular and genomic studies of IMMP2L and mutation screening in autism and Tourette syndrome. Mol. Genet. Genomics 277, 71–81 (2007).

    CAS  PubMed  Google Scholar 

  49. Patel, C. et al. Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome. Eur. J. Hum. Genet. 19, 634–639 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Lu, B. et al. A mutation in the inner mitochondrial membrane peptidase 2-like gene (Immp2l) affects mitochondrial function and impairs fertility in mice. Biol. Reprod. 78, 601–610 (2008).

    CAS  PubMed  Google Scholar 

  51. Ma, Y., Mehta, S. L., Lu, B. & Li, P. A. Deficiency in the inner mitochondrial membrane peptidase 2-like (Immp21) gene increases ischemic brain damage and impairs mitochondrial function. Neurobiol. Dis. 44, 270–276 (2011).

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Leonard, J. V. & Schapira, A. H. Mitochondrial respiratory chain disorders II: neurodegenerative disorders and nuclear gene defects. Lancet 355, 389–394 (2000).

    CAS  PubMed  Google Scholar 

  53. Whatley, S. A., Curti, D. & Marchbanks, R. M. Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem. Res. 21, 995–1004 (1996).

    CAS  PubMed  Google Scholar 

  54. Belloso, J. M. et al. Disruption of the CNTNAP2 gene in a t(7;15) translocation family without symptoms of Gilles de la Tourette syndrome. Eur. J. Hum. Genet. 15, 711–713 (2007).

    CAS  PubMed  Google Scholar 

  55. Poot, M. et al. Disruption of CNTNAP2 and additional structural genome changes in a boy with speech delay and autism spectrum disorder. Neurogenetics 11, 81–89 (2010).

    PubMed  Google Scholar 

  56. Chou, I. C., Wan, L., Liu, S. C., Tsai, C. H. & Tsai, F. J. Association of the Slit and Trk-like 1 gene in Taiwanese patients with Tourette syndrome. Pediatr. Neurol. 37, 404–406 (2007).

    PubMed  Google Scholar 

  57. Deng, H., Le, W. D., Xie, W. J. & Jankovic, J. Examination of the SLITRK1 gene in Caucasian patients with Tourette syndrome. Acta Neurol. Scand. 114, 400–402 (2006).

    CAS  PubMed  Google Scholar 

  58. Fabbrini, G. et al. A large Italian family with Gilles de la Tourette syndrome: clinical study and analysis of the SLITRK1 gene. Mov. Disord. 22, 2229–2234 (2007).

    PubMed  Google Scholar 

  59. Orth, M. et al. Autosomal dominant myoclonus-dystonia and Tourette syndrome in a family without linkage to the SGCE gene. Mov. Disord. 22, 2090–2096 (2007).

    PubMed  Google Scholar 

  60. Pasquini, M. et al. Psychopathological features of obsessive–compulsive disorder in an Italian family with Gilles de la Tourette syndrome not linked to the SLITRK1 gene. Psychiatry Res. 161, 109–111 (2008).

    CAS  PubMed  Google Scholar 

  61. Verkerk, A. J. et al. Genetic and clinical analysis of a large Dutch Gilles de la Tourette family. Mol. Psychiatry 11, 954–964 (2006).

    CAS  PubMed  Google Scholar 

  62. Zimprich, A. et al. Sequence analysis of the complete SLITRK1 gene in Austrian patients with Tourette's disorder. Psychiatr. Genet. 18, 308–309 (2008).

    PubMed  Google Scholar 

  63. Keen-Kim, D. et al. Overrepresentation of rare variants in a specific ethnic group may confuse interpretation of association analyses. Hum. Mol. Genet. 15, 3324–3328 (2006).

    CAS  PubMed  Google Scholar 

  64. Scharf, J. M. et al. Lack of association between SLITRK1 var321 and Tourette syndrome in a large family-based sample. Neurology 70, 1495–1496 (2008).

    CAS  PubMed  Google Scholar 

  65. Wendland, J. R., Kruse, M. R. & Murphy, D. L. Functional SLITRK1 var321, varCDfs and SLC6A4 G56A variants and susceptibility to obsessive–compulsive disorder. Mol. Psychiatry 11, 802–804 (2006).

    CAS  PubMed  Google Scholar 

  66. Miranda, D. M. et al. Association of SLITRK1 to Gilles de la Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 483–486 (2009).

    CAS  PubMed  Google Scholar 

  67. O'Roak, B. J. et al. Additional support for the association of SLITRK1 var321 and Tourette syndrome. Mol. Psychiatry 15, 447–450 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Aruga, J. & Mikoshiba, K. Identification and characterization of Slitrk, a novel neuronal transmembrane protein family controlling neurite outgrowth. Mol. Cell Neurosci. 24, 117–129 (2003).

    CAS  PubMed  Google Scholar 

  69. Kajiwara, Y., Buxbaum, J. D. & Grice, D. E. SLITRK1 binds 14-3-3 and regulates neurite outgrowth in a phosphorylation-dependent manner. Biol. Psychiatry 66, 918–925 (2009).

    CAS  PubMed  Google Scholar 

  70. Stillman, A. A. et al. Developmentally regulated and evolutionarily conserved expression of SLITRK1 in brain circuits implicated in Tourette syndrome. J. Comp. Neurol. 513, 21–37 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Katayama, K. et al. Slitrk1-deficient mice display elevated anxiety-like behavior and noradrenergic abnormalities. Mol. Psychiatry 15, 177–184 (2010).

    CAS  PubMed  Google Scholar 

  72. Devor, E. J. & Magee, H. J. Multiple childhood behavioral disorders (Tourette syndrome, multiple tics, ADD and OCD) presenting in a family with a balanced chromosome translocation (t1;8)(q21.1;q22.1). Psychiatr. Genet. 9, 149–151 (1999).

    CAS  PubMed  Google Scholar 

  73. Matsumoto, N. et al. Breakpoint sequences of an 1;8 translocation in a family with Gilles de la Tourette syndrome. Eur. J. Hum. Genet. 8, 875–883 (2000).

    CAS  PubMed  Google Scholar 

  74. Crawford, F. C. et al. Translocation breakpoint in two unrelated Tourette syndrome cases, within a region previously linked to the disorder. Hum. Genet. 113, 154–161 (2003).

    CAS  PubMed  Google Scholar 

  75. Singh, D. N., Howe, G. L., Jordan, H. W. & Hara, S. Tourette's syndrome in a black woman with associated triple X and 9p mosaicism. J. Natl Med. Assoc. 74, 675–682 (1982).

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Taylor, L. D. et al. 9p monosomy in a patient with Gilles de la Tourette's syndrome. Neurology 41, 1513–1515 (1991).

    CAS  PubMed  Google Scholar 

  77. Jankovic, J. & Deng, H. Candidate locus for chorea and tic disorders at 15q? Pediatr. Neurol. 37, 70–73 (2007).

    PubMed  Google Scholar 

  78. Kerbeshian, J., Severud, R., Burd, L. & Larson, L. Peek-a-boo fragile site at 16d associated with Tourette syndrome, bipolar disorder, autistic disorder, and mental retardation. Am. J. Med. Genet. 96, 69–73 (2000).

    CAS  PubMed  Google Scholar 

  79. Shelley, B. P., Robertson, M. M. & Turk, J. An individual with Gilles de la Tourette syndrome and Smith–Magenis microdeletion syndrome: is chromosome 17p11.2 a candidate region for Tourette syndrome putative susceptibility genes? J. Intellect. Disabil. Res. 51, 620–624 (2007).

    CAS  PubMed  Google Scholar 

  80. Dehning, S., Riedel, M. & Muller, N. Father-to-son transmission of 6;17 translocation in Tourette's syndrome. Am. J. Psychiatry 165, 1051–1052 (2008).

    PubMed  Google Scholar 

  81. Robertson, M. M., Shelley, B. P., Dalwai, S., Brewer, C. & Critchley, H. D. A patient with both Gilles de la Tourette's syndrome and chromosome 22q11 deletion syndrome: clue to the genetics of Gilles de la Tourette's syndrome? J. Psychosom. Res. 61, 365–368 (2006).

    PubMed  Google Scholar 

  82. Clarke, R. A., Fang, Z. M., Diwan, A. D. & Gilbert, D. L. Tourette syndrome and Klippel–Feil anomaly in a child with chromosome 22q11 duplication. Case Report Med. http://dx.doi.org/10.1155/2009/361518.

  83. Donnai, D. Gene location in Tourette syndrome. Lancet 1, 627 (1987).

    CAS  PubMed  Google Scholar 

  84. Cuker, A., State, M. W., King, R. A., Davis, N. & Ward, D. C. Candidate locus for Gilles de la Tourette syndrome/obsessive compulsive disorder/chronic tic disorder at 18q22. Am. J. Med. Genet. A 130A, 37–39 (2004).

    PubMed  Google Scholar 

  85. State, M. W. et al. Epigenetic abnormalities associated with a chromosome 18(q21–q22) inversion and a Gilles de la Tourette syndrome phenotype. Proc. Natl Acad. Sci. USA 100, 4684–4689 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Brett, P. M., Curtis, D., Robertson, M. M. & Gurling, H. M. Neuroreceptor subunit genes and the genetic susceptibility to Gilles de la Tourette syndrome. Biol. Psychiatry 42, 941–947 (1997).

    CAS  PubMed  Google Scholar 

  87. Kubota, Y. et al. Increased methamphetamine-induced locomotor activity and behavioral sensitization in histamine-deficient mice. J. Neurochem. 83, 837–845 (2002).

    CAS  PubMed  Google Scholar 

  88. Haas, H. L., Sergeeva, O. A. & Selbach, O. Histamine in the nervous system. Physiol. Rev. 88, 1183–1241 (2008).

    CAS  PubMed  Google Scholar 

  89. Bloch, M., State, M. & Pittenger, C. Recent advances in Tourette syndrome. Curr. Opin. Neurol. 24, 119–125 (2011).

    PubMed Central  PubMed  Google Scholar 

  90. Lei, J. et al. Mutation screening of the HDC gene in Chinese Han patients with Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 159B, 72–76 (2012).

    PubMed  Google Scholar 

  91. Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R. & Cowart, M. D. Discovery of histamine H3 antagonists for the treatment of cognitive disorders and Alzheimer's disease. J. Pharmacol. Exp. Ther. 336, 38–46 (2011).

    CAS  PubMed  Google Scholar 

  92. Knight, S. et al. Linkage analysis of Tourette syndrome in a large Utah pedigree. Am. J. Med. Genet. B Neuropsychiatr. Genet. 153B, 656–662 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Curtis, D. et al. Genome scan of Tourette syndrome in a single large pedigree shows some support for linkage to regions of chromosomes 5, 10 and 13. Psychiatr. Genet. 14, 83–87 (2004).

    CAS  PubMed  Google Scholar 

  94. Laurin, N., Wigg, K. G., Feng, Y., Sandor, P. & Barr, C. L. Chromosome 5 and Gilles de la Tourette syndrome: Linkage in a large pedigree and association study of six candidates in the region. Am. J. Med. Genet. B Neuropsychiatr. Genet. 150B, 95–103 (2009).

    CAS  PubMed  Google Scholar 

  95. Simonic, I., Gericke, G. S., Ott, J. & Weber, J. L. Identification of genetic markers associated with Gilles de la Tourette syndrome in an Afrikaner population. Am. J. Hum. Genet. 63, 839–846 (1998).

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Simonic, I. et al. Further evidence for linkage of Gilles de la Tourette syndrome (GTS) susceptibility loci on chromosomes 2p11, 8q22 and 11q23–24 in South African Afrikaners. Am. J. Med. Genet. 105, 163–167 (2001).

    CAS  PubMed  Google Scholar 

  97. Barr, C. L. et al. Genome scan for linkage to Gilles de la Tourette syndrome. Am. J. Med. Genet. 88, 437–445 (1999).

    CAS  PubMed  Google Scholar 

  98. The Tourette Syndrome Association for Genetics. A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. Am. J. Hum. Genet. 65, 1428–1436 (1999).

  99. Zhang, H. et al. Genomewide scan of hoarding in sib pairs in which both sibs have Gilles de la Tourette syndrome. Am. J. Hum. Genet. 70, 896–904 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  100. Feng, R., Leckman, J. F. & Zhang, H. Linkage analysis of ordinal traits for pedigree data. Proc. Natl Acad. Sci. USA 101, 16739–16744 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. The Tourette Syndrome Association for Genetics. Genome scan for Tourette disorder in affected-sibling-pair and multigenerational families. Am. J. Hum. Genet. 80, 265–272 (2007).

  102. Horn, S. Gilles de la Tourette syndrome. Clin. Neuropharmacol. 24, 125–128 (2001).

    CAS  PubMed  Google Scholar 

  103. Comings, D. E. Clinical and molecular genetics of ADHD and Tourette syndrome. Two related polygenic disorders. Ann. NY Acad. Sci. 931, 50–83 (2001).

    CAS  PubMed  Google Scholar 

  104. Cerullo, J., Reimschisel. T. & Singer, H. in Genetic and neurobiological basis for Tourette syndrome. Treating Tourette Syndrome and Tic Disorders: A Guide for Practitioners (eds Woods, D. W. et al.) 58–84 (Guilford Press, New York, 2007).

    Google Scholar 

  105. Leckman, J. F. Tourette's syndrome. Lancet 360, 1577–1586 (2002).

    PubMed  Google Scholar 

  106. Talebizadeh, Z. et al. Novel splice isoforms for NLGN3 and NLGN4 with possible implications in autism. J. Med. Genet. 43, e21 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Blasi, F. et al. Absence of coding mutations in the X-linked genes neuroligin 3 and neuroligin 4 in individuals with autism from the IMGSAC collection. Am. J. Med. Genet. B Neuropsychiatr. Genet. 141B, 220–221 (2006).

    CAS  PubMed  Google Scholar 

  108. Zhang, C. et al. A neuroligin-4 missense mutation associated with autism impairs neuroligin-4 folding and endoplasmic reticulum export. J. Neurosci. 29, 10843–10854 (2009).

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Riviere, J. B. et al. Association of intronic variants of the BTBD9 gene with Tourette syndrome. Arch. Neurol. 66, 1267–1272 (2009).

    PubMed  Google Scholar 

  110. Dehning, S. et al. A genetic variant of HTR2C may play a role in the manifestation of Tourette syndrome. Psychiatr. Genet. 20, 35–38 (2010).

    PubMed  Google Scholar 

  111. Bevilacqua, L. et al. A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature 468, 1061–1066 (2010).

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Crane, J. et al. Family-based genetic association study of DLGAP3 in Tourette syndrome. Am. J. Med. Genet. B Neuropsychiatr. Genet. 156B, 108–114 (2011).

    PubMed  Google Scholar 

  113. Sundaram, S. K. et al. Exome sequencing of a pedigree with Tourette syndrome or chronic tic disorder. Ann. Neurol. 69, 901–904 (2011).

    CAS  PubMed  Google Scholar 

  114. Jankovic, J. & Mejia, N. I. Tics associated with other disorders. Adv. Neurol. 99, 61–68 (2006).

    PubMed  Google Scholar 

  115. Romstad, A. et al. Dopa-responsive dystonia and Tourette syndrome in a large Danish family. Arch. Neurol. 60, 618–622 (2003).

    PubMed  Google Scholar 

  116. Yaltho, T. C., Jankovic, J. & Lotze, T. The association of Tourette syndrome and dopa-responsive dystonia. Mov. Disord. 26, 359–360 (2011).

    PubMed  Google Scholar 

  117. Orstavik, R. E., Tommerup, N., Eiklid, K. & Orstavik, K. H. Non-random X chromosome inactivation in an affected twin in a monozygotic twin pair discordant for Wiedemann-Beckwith syndrome. Am. J. Med. Genet. 56, 210–214 (1995).

    CAS  PubMed  Google Scholar 

  118. Sykiotis, G. P. et al. Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. Proc. Natl Acad. Sci. USA 107, 15140–15144 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Diaz-Anzaldua, A. et al. Tourette syndrome and dopaminergic genes: a family-based association study in the French Canadian founder population. Mol. Psychiatry 9, 272–277 (2004).

    CAS  PubMed  Google Scholar 

  120. Toft, M., Mata, I. F., Kachergus, J. M., Ross, O. A. & Farrer, M. J. LRRK2 mutations and Parkinsonism. Lancet 365, 1229–1230 (2005).

    PubMed  Google Scholar 

  121. Lesch, K. P. et al. Genome-wide copy number variation analysis in attention-deficit/hyperactivity disorder: association with neuropeptide Y gene dosage in an extended pedigree. Mol. Psychiatry 16, 491–503 (2011).

    CAS  PubMed  Google Scholar 

  122. Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Sundaram, S. K., Huq, A. M., Wilson, B. J. & Chugani, H. T. Tourette syndrome is associated with recurrent exonic copy number variants. Neurology 74, 1583–1590 (2010).

    PubMed Central  PubMed  Google Scholar 

  124. Grados, M. A. The genetics of obsessive–compulsive disorder and Tourette syndrome: an epidemiological and pathway-based approach for gene discovery. J. Am. Acad. Child. Adolesc. Psychiatry 49, 810–819 (2010).

    PubMed  Google Scholar 

  125. So, H. C., Li, M. & Sham, P. C. Uncovering the total heritability explained by all true susceptibility variants in a genome-wide association study. Genet. Epidemiol. 35, 447–456 (2011).

    PubMed  Google Scholar 

  126. Deng, H., Gu, S., Jankovic, J. LINGO1 variants in essential tremor and Parkinson's disease. Acta Neurol. Scand. 125, 1–7 (2012).

    CAS  PubMed  Google Scholar 

  127. Merette, C. et al. Significant linkage for Tourette syndrome in a large French Canadian family. Am. J. Hum. Genet. 67, 1008–1013 (2000).

    CAS  PubMed Central  PubMed  Google Scholar 

  128. Breedveld, G. J., Fabbrini, G., Oostra, B. A., Berardelli, A. & Bonifati, V. Tourette disorder spectrum maps to chromosome 14q31.1 in an Italian kindred. Neurogenetics 11, 417–423 (2010).

    PubMed Central  PubMed  Google Scholar 

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Acknowledgements

Hao Deng was supported by National Natural Science Foundation of China (30871351), Sheng Hua Scholars Program and Outstanding Youth Foundation of Central South University, China, the Fundamental Research Funds for the Central Universities (2011JQ014), Program for New Century Excellent Talents in University of Ministry of Education of P. R. China (NCET-080563), Research Fund for the Doctoral Program of Higher Education of China (20110162110026) and Grant for the Foster Key Subject of the Third Xiangya Hospital (Clinical Laboratory Diagnostics). Kai Gao was supported by Mittal Students Innovative Projects of Central South University, China (11MX28). Joseph Jankovic was supported by the Diana Helis Henry Medical Research Foundation, the National Parkinson Foundation and Huntington Disease Society of America, Baylor College of Medicine Center of Excellence.

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Authors and Affiliations

  1. Center for Experimental Medicine, the Third Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha, 410013, Hunan, China

    Hao Deng & Kai Gao

  2. Department of Neurology, Baylor College of Medicine, 6550 Fannin Street, NB302, Houston, 77030, TX, USA

    Joseph Jankovic

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  1. Hao Deng
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H. Deng, K. Gao and J. Jankovic researched the data for the article, provided substantial contributions to discussions of content, and contributed equally to writing the article and to reviewing and editing of the manuscript before submission.

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Correspondence to Hao Deng.

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Deng, H., Gao, K. & Jankovic, J. The genetics of Tourette syndrome. Nat Rev Neurol 8, 203–213 (2012). https://doi.org/10.1038/nrneurol.2012.26

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